A tyrosine-based signal present in Ig alpha mediates B cell receptor constitutive internalization.
B lymphocytes express Ag receptors (BCR) that are composed of ligand binding subunits, the membrane Igs, associated with Ig alpha/Ig beta heterodimers. One main BCR function is to bind and to internalize Ags. Peptides generated from these internalized Ags may be presented to T lymphocytes. Here, we have analyzed the involvement of BCR Ig alpha/Ig beta components in BCR constitutive endocytosis. The role of Ig alpha subunit in BCR constitutive endocytosis was first determined in the context of an IgM-based BCR. In contrast with BCR that contain wild-type Ig alpha, surface BCR lacking Ig alpha cytoplasmic domain were not constitutively internalized. The respective roles of Ig alpha and Ig beta subunits were then analyzed by expressing chimeric molecules containing the cytoplasmic domains of either subunits in a B cell line. Only the Ig alpha cytoplasmic domain contained an internalization signal that allowed constitutive endocytosis of Ig alpha chimeras via coated pits and accumulation in sorting-recycling endosomes. This internalization signal is contained in its immunoreceptor tyrosine-based activation motif. These results indicate that Ig alpha, through its immunoreceptor tyrosine-based activation motif, may account for the ability of IgM/IgD BCR to constitutively internalize monovalent Ags.
Cassard
S
S
CJF 9501, INSERM, Institut Curie, Paris, France.
Salamero
J
J
Hanau
D
D
Spehner
D
D
Davoust
J
J
Fridman
W H
WH
Bonnerot
C
C
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D051925:CD79 Antigens; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000276:immunology*; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D016393:Lymphoma, B-Cell; D051379:Mice; D008969:Molecular Sequence Data; D017459:Receptors, Amino Acid / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000276:immunology / Q000502:physiology*
D015703:Antigens, CD; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D017459:Receptors, Amino Acid; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D014168:Transferrin; C087659:tyrosine receptor; D014443:Tyrosine